Homing and Function of Human Skin γδ T Cells and NK Cells: Relevance for Tumor Surveillance

Abstract

Normal (noninflamed) human skin contains a network of lymphocytes, but little is known about the homing and function of these cells. The majority of αβ T cells in normal skin express CCR8 and produce proinflammatory cytokines. In this study we examined other subsets of cutaneous lymphocytes, focusing on those with potential function in purging healthy tissue of transformed and stressed cells. Human dermal cell suspensions contained significant populations of Vδ1+ γδ T cells and CD56+CD16− NK cells, but lacked the subsets of Vδ2+ γδ T cells and CD56+CD16+ NK cells, which predominate in peripheral blood. The skin-homing receptors CCR8 and CLA were expressed by a large fraction of both cell types, whereas chemokine receptors associated with lymphocyte migration to inflamed skin were absent. Neither cell type expressed CCR7, although γδ T cells up-regulated this lymph node-homing receptor upon TCR triggering. Stimulation of cutaneous Vδ1+ γδ T cell lines induced secretion of large amounts of TNF-α, IFN-γ, and the CCR8 ligand CCL1. In contrast to cutaneous αβ T cells, both cell types had the capacity to produce intracellular perforin and displayed strong cytotoxic activity against melanoma cells. We therefore propose that γδ T cells and NK cells are regular constituents of normal human skin with potential function in the clearance of tumor and otherwise stressed tissue cells.

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

“…44 NK cells are usually rare in healthy skin. [45][46][47] This limits access to HPV-infected cells and reflects a minor role of NK cells in the natural HPV life cycle within the epidermis. However, during cancer growth infected cells come into reach for NK cell killing.…”

“…Extracted DNA was analyzed for mucosal high risk HPV-DNA and HPV genotypes (16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 68, 73 and 82) by PCR optimized for DNA extracted from FFPE tissue, followed by bead-based hybridization (Luminex technology, Multimetrix, Progen, Heidelberg), as described previously. 17,18 HPV-DNA contamination protection steps (e.g., new microtome blades for every block, separated pre and post PCR areas) were applied and appropriate controls (tissue-free paraffin blocks, water-controls) were processed to monitor potential high risk HPV-DNA contamination.…”

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood

“…Nevertheless, this preliminary experiment provides novel evidence that NK cells are found in the skin of calves and therefore suggests that NK cells can migrate from the skin, through afferent lymphatic vessels and into the LNs. In humans, CD56 bright CD16 − NK cells are present in the dermis of healthy skin and were also found in skin from patients with atopic eczema/dermatitis, where they were in close contact with CD1a + dendritic cells 34, 35…”

Select Plant Tannins Induce IL-2Rα Up-Regulation and Augment Cell Division in γδ T Cells

“…V␦2 T cells are potent antimicrobial and antitumor effector cells (9 -11). V␦1 cells have important immunoregulatory functions and, if properly stimulated, can become potent effector cells (12).…”

“…Though expansion of V␦2 T cells in vivo is clearly demonstrated using these new drugs, the benefit of these expanded cells on host defenses is not fully understood due to a minimal or nonexistent response in non-primate animal models (19). Additional caveats for the clinical use of phosphoantigen-based drugs include the requirement for large amounts of agonist (20), induction of rapid cell anergy to treatment (20), and activation of only the V␦2 subset, which must then traffic to the tumor or infection to be effective (8,12,20,21).…”